Iron is an essential nutrient for virtually all cells, including mammalian cells, but iron is a double-edge sword. Iron is an essential element for oxygen transport and numerous biochemical reactions, including oxidation/reduction activity. Excess iron is toxic, causing cellular dysfunction, presumably due to the generation of highly toxic free radicals that can damage all molecular classes found in vivo. Therefore, proper iron regulation is crucial for the health of a subject, including a mammal, such as a human.
Iron produces free radicals, which are highly reactive atoms or groups of atoms that have one or more unpaired electrons. This free radical damage has long been believed to be a risk factor for the degenerative processes that accompany aging in a variety of animal species ranging from insects to humans. These include Alzheimer's and Parkinson's disease, coronary vascular diseases, inflammation and inflammatory disease and other diseases.1-4 The significant increases are also suggested, albeit controversially, to pose a risk for several chronic diseases, including, heart disease, cancer, diabetes, metabolic disorders associated with insulin resistance syndrome, atherosclerosis, and aging.5-13 
Because of the long retention time of iron (half life of about 5.5 years), and the lack of a major mechanism of iron excretion in human body, iron accumulation in tissues is a characteristic of aging organisms, despite the fact that some studies show almost no change in the iron concentrations in healthy male livers associated with aging.14-16 Stored body iron, for example, as estimated by serum ferritin (SF) measurement, increases rapidly after menopause in women and adolescence in men. The increase continues with age and reaches a plateau in about the sixth decade of life. In postmenopausal women, the mean level of storage iron, as reflected by SF concentrations, is 106.3 ng/mL, more than twice that in premenopausal women with 43.0 ng/mL.17 As will be recognized, postmenopausal osteoporosis is a disease that correlates with the increased mean level of storage iron.
Iron accumulation is also found in adult men, where the mean concentration of serum ferritin (SF) is 121 ng/mL, while males aged from 5 to 19 have a concentration of around 20 to 30 ng/mL.
Therefore, free radical formation may play a role in many diseases. For example, Alzheimer's disease, Parkinson's disease, coronary vascular diseases, inflammation and inflammatory disease, heart disease, cancer, diabetes metabolic disorders associated with insulin resistance syndrome, atherosclerosis, and aging.
While the relationship between free radical formation and diseases in skeletal tissues in situ is poorly understood, studies are also beginning to show a connection between free radical damage and skeletal diseases, such as osteoporosis. For instance, a mitochrondrial DNA deletion has been associated with systemic oxidative stress and severe osteoporosis in human males.18 Furthermore, antioxidant administration (e.g., vitamin E or citrus flavonoid) increases the bone mass of animals.19-20 
With the widespread and diverse implications for iron accumulation in vivo, there is a need in the art for treatments that may reduce, prevent or treat disease commonly associated with increased iron concentrations. Two examples of such diseases are osteoporosis and Alzheimer's disease.
Postmenopausal osteoporosis is a disease in which bones lose strength leading to an increased risk of fracture. One in two women over age 50 will have an osteoporosis-related fracture during their lives. Moreover, in the United States there are millions of women who have osteopenia, placing them at increased risk for postmenopausal osteoporosis. This disease has presented a big health problem not only for the United States, but also worldwide because approximately 200 million women suffer from this disease and it is increasing in significance as the population of the world both grows and ages. Also, postmenopausal osteoporosis and associated fractures put a heavy economic burden on society because of disability, decreased quality of life, and mortality. According to the International Osteoporosis Foundation, annual direct medical costs to treat 2.3 million osteoporosis fractures in Europe and in the United States of America are about $27 billion.
Furthermore, the lifetime risk of dying from osteoporotic hip fractures alone (about 20% of all osteoporotic fractures (NIH)) is the same as that of dying from breast cancer, and the risk of osteoporosis is greater than breast, cervical and endometrial cancer combined.
Alzheimer's disease (AD) is a progressive, degenerative, and irreversible brain disorder that is ultimately fatal. It is the most common form of dementia among people age 65 and older.21 Currently, about 4 million Americans suffer with the disease and approximately 360,000 new cases will occur each year. AD presents a big health problem, not only for the USA, but also worldwide, because of its enormous impact on individuals, families, the health care system, and society as a whole. The annual national cost of caring for AD patients has been estimated to be over $100 billion. Unfortunately, there is no known cure for AD at the present time.
Presently only acetylcholinesterase inhibiting drugs are approved by the Food and Drug Administration for treatment of AD in the US; they are Aricept (donepezil), Cognex (tacrine), Rivastigmine (Exelon), and Galantamine (Reminyl, also acting as an allosterically potentiating ligand on nicotinic acetylcholine receptors).21-23 Although treatment with these drugs provides symptomatic improvements or delays in the progression of cognitive, behavioral, and functional deficits, it does not stop or reverse the progression of AD.
Other methods of treatment that have received some attention include anti-inflammatory drugs18, antioxidants24, estrogen, and nerve growth factor.21 Therefore, there remains a strong need in the art for additional treatment methods.
Accumulating evidence supports the hypothesis that oxidative stress generated by various mechanisms may be among the major intermediary risk factors that initiate and promote neurodegeneration in AD.25-28 Many reports show that the metabolism of iron is involved in AD and that the concentration of iron in the brain of AD patients is elevated.29 Smith et al. studied the distribution of iron in the brain of AD patients using various histochemical methods and observed that the iron distribution matched the distribution of senile plaques (SP) and neurofibrillary tangles (NFT), the two hallmark pathologies of AD.8,10 Aluminum (Al) has also been shown to accumulate in the central nervous system and modulate the formation and deposition of Aβ in the brain [161]. Al, unlike transition metal ions, is unable to redox cycle in electron transfer reactions due to a fixed oxidation state of 3+ in biological systems, but growing evidence suggests that it can act synergistically with iron to increase free radical damage.30 Strong evidence also shows that other metals are implicated in the development of AD, including, but not limited to, copper and zinc.31-38 
Overall, these studies indicate that the environment in the brain in AD, due to imbalances of several metal elements has the potential of catalyzing and stimulating free radical formation and enhancing neuron degeneration.
The elevated concentration of so many metals has previously looked too complex to be dealt with. However, the invention provides a unique opportunity for chelation therapy for the treatment of numerous diseases, including, but not limited to, AD and osteoporosis.